Abstract
INTRODUCTION: The β-thalassemias are inherited genetic disorders affecting the hematopoietic system and caused by mutations of the adult β-globin gene, leading to low or absent production of adult hemoglobin. In addition, an excess of free α-globin is associated with ineffective erythropoiesis. In fact, the free α-globin molecules are prone to precipitate, causing toxicity to the erythroid cells, and interference with red cell maturation. In order to counteract the detrimental effects of the excess of α-globin, two pathways might be activated in β-thalassemia erythroid cells, i.e. Unc-51-like kinase 1 (Ulk-1)-mediated induction of autophagy and increased expression of the α-hemoglobin stabilizing protein (AHSP). CASE PRESENTATION: The studied case was a male transfusion dependent TM (Thalassemia Major) patient, aged 43 years, with a β(0)39/β(+)IVSI-110 genotype (XmnI polymorphism: -/-), starting the first blood transfusion when he was 5 months old, and participating to the NCT03877809 (Sirthalaclin) clinical trial. METHODS: Expression of AHSP and Ulk-genes in Erythroid precursor cells (ErPCs) was studied by Reverse transcription (RT)-qPCR and Western blotting ErPCs were isolated from the propositus after 90 and 180 days of treatment with sirolimus. RESULTS AND DISCUSSION: This study demonstrates for the first time that increase in the production of γ-globin2 mRNA and HbF in ErPCs from a patient with β-thalassemia treated with sirolimus might be associated with co-induction of Ulk-1 and AHSP genes.